Long-Term Clinical Outcomes of Patients with Drug-Induced Type 1 Brugada Electrocardiographic Pattern: A Nationwide Cohort Registry Study

Background: There are limited real-world data about the extended prognosis of patients with drug-induced type 1 Brugada electrocardiogram (ECG). Objective: We assessed the clinical outcomes and predictors of life-threatening arrhythmias in patients with drug-induced type 1 Brugada ECG. Materials and methods: This multicenter retrospective study, conducted at 21 Italian and Swiss hospitals from July 1997 to May 2021, included consecutive patients with drug-induced type 1 ECG. The primary outcome, a composite of appropriate ICD therapies and sudden cardiac death (SCD), was assessed along with the clinical predictors of these events. Results: A total of 606 patients (mean age 49.7±14.7 years; 69.8% men) were followed up for a median of 60.3 [23.0-122.4] months. Nineteen patients (3.1%) experienced life-threatening arrhythmias, with a median annual event rate of 0.5% over 5 years and 0.25% over 10 years. The SCN5A mutation was the only predictor of primary outcome (HR: 4.54, p= 0.002); whereas a trend was observed for unexplained syncope (HR: 3.85; p= 0.05). Among patients who were asymptomatic at presentation, the median annual rate of life-threatening arrhythmias is 0.24% over 5 years and increases to 1.2% if they have inducible ventricular fibrillation (VF) during programmed ventricular stimulation (PVS). Conclusion: In drug-induced type 1 Brugada ECG patients, the annual risk of life-threatening arrhythmias is low, with the SCN5A mutation as the only independent predictor. The unexplained syncope correlated with worse clinical outcomes. The VF inducibility at PVS significantly increases the median annual rate of life-threatening arrhythmias from 0.24% to 1.2% over 5 years.